keyword
MENU ▼
Read by QxMD icon Read
search

TAK1

keyword
https://www.readbyqxmd.com/read/28045080/transforming-growth-factor-%C3%AE-activated-kinase-1-transcriptionally-suppresses-hepatitis-b-virus-replication
#1
Jinke Pang, Geng Zhang, Yong Lin, Zhanglian Xie, Hongyan Liu, Libo Tang, Mengji Lu, Ran Yan, Haitao Guo, Jian Sun, Jinlin Hou, Xiaoyong Zhang
Hepatitis B Virus (HBV) replication in hepatocytes is restricted by the host innate immune system and related intracellular signaling pathways. Transforming growth factor β-activated kinase 1 (TAK1) is a key mediator of toll-like receptors and pro-inflammatory cytokine signaling pathways. Here, we report that silencing or inhibition of endogenous TAK1 in hepatoma cell lines leads to an upregulation of HBV replication, transcription, and antigen expression. In contrast, overexpression of TAK1 significantly suppresses HBV replication, while an enzymatically inactive form of TAK1 exerts no effect...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28043920/altered-mir-370-expression-in-hepatic-ischemia-reperfusion-injury-correlates-with-the-level-of-nuclear-kappa-b-nf-%C3%AE%C2%BAb-related-factors
#2
Jie Zhu, Fangfang Zhu, Wenfeng Song, Bin Zhang, Xie Zhang, Xiaofeng Jin, Hong Li
BACKGROUND & AIMS: MicroRNAs (miRNAs) are a class of small endogenous, non-coding RNAs that regulate gene expression at both the transcription and translation levels. Whether miRNAs have taken part in liver ischemia-reperfusion (IR) injury was rarely reported. The purpose of this article is to investigate the potential role of miR-370 in hepatic IR injury. METHODS: Male C57BL/6 mice were divided into 5 groups (sham-operated group, I/R group, IPC group, antagomir-370 group and antagomir-NC), and the expression levels of miR-370 were assessed by quantitative real-time PCR...
December 30, 2016: Gene
https://www.readbyqxmd.com/read/28039475/gpr120-a-potential-therapeutic-target-for-experimental-colitis-in-il-10-deficient-mice
#3
Jie Zhao, Honggang Wang, Peiliang Shi, Wenbo Wang, Ye Sun
It has been proved that interleukin-10-knockout (IL-10 KO) mice display the most similar characteristics to that of human Crohn's disease (CD). Docosahexaenoic acid (DHA) has well established beneficial effects on human and animal models health with potent anti-inflammatory effects with poorly understood mechanisms. This study was aimed at figuring out whether DHA could ameliorate the Crohn's colitis by activating GPR120 and whether GPR120 could be a potential therapeutic target for CD.16 week-old mice included in our present study were divided into three groups, WT group, IL-10 KO group and DHA group(IL-10 KO mice with DHA treatment, i...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28038940/studies-of-tak1-centered-polypharmacology-with-novel-covalent-tak1-inhibitors
#4
Li Tan, Deepak Gurbani, Ellen L Weisberg, Douglas S Jones, Suman Rao, William D Singer, Faviola M Bernard, Samar Mowafy, Annie Jenney, Guangyan Du, Atsushi Nonami, James D Griffin, Douglas A Lauffenburger, Kenneth D Westover, Peter K Sorger, Nathanael S Gray
Targeted polypharmacology provides an efficient method of treating diseases such as cancer with complex, multigenic causes provided that compounds with advantageous activity profiles can be discovered. Novel covalent TAK1 inhibitors were validated in cellular contexts for their ability to inhibit the TAK1 kinase and for their polypharmacology. Several inhibitors phenocopied reported TAK1 inhibitor 5Z-7-oxozaenol with comparable efficacy and complementary kinase selectivity profiles. Compound 5 exhibited the greatest potency in RAS-mutated and wild-type RAS cell lines from various cancer types...
December 7, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28013046/loss-of-tradd-attenuates-pressure-overload-induced-cardiac-hypertrophy-through-regulating-tak1-p38-mapk-signalling-in-mice
#5
Lianpin Wu, Zhiyong Cao, Liqin Mei, Ling Ji, Qike Jin, Jingjing Zeng, Jiafeng Lin, Maoping Chu, Lei Li, Xiangjun Yang
We investigated the role of tumour necrosis factor receptor (TNFR)-associated death domain (TRADD) on pressure overload-induced cardiac hypertrophy and the underlying molecular mechanisms by using a TRADD deficiency mice model. 6-8 weeks wild-type and TRADD knockout mice were performed to transverse aorta constriction (TAC) or sham operation (6-8 mice for each group). 14 days after TAC, cardiac function was measured by echocardiography, as well as by pathological and molecular analyses of heart samples. The expressions of cardiac hypertrophic and fibrotic markers were detected by qPCR...
December 21, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28011204/structure-guided-development-of-covalent-tak1-inhibitors
#6
Li Tan, Deepak Gurbani, Ellen L Weisberg, John C Hunter, Lianbo Li, Douglas S Jones, Scott B Ficarro, Samar Mowafy, Chun-Pong Tam, Suman Rao, Guangyan Du, James D Griffin, Peter K Sorger, Jarrod A Marto, Kenneth D Westover, Nathanael S Gray
TAK1 (transforming growth factor-β-activated kinase 1) is an essential intracellular mediator of cytokine and growth factor signaling and a potential therapeutic target for the treatment of immune diseases and cancer. Herein we report development of a series of 2,4-disubstituted pyrimidine covalent TAK1 inhibitors that target Cys174, a residue immediately adjacent to the 'DFG-motif' of the kinase activation loop. Co-crystal structures of TAK1 with candidate compounds enabled iterative rounds of structure-based design and biological testing to arrive at optimized compounds...
December 9, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27995356/tripartite-motif-8-trim8-positively-regulates-pro-inflammatory-responses-in-pseudomonas-aeruginosa-induced-keratitis-through-promoting-k63-linked-polyubiquitination-of-tak1-protein
#7
Litao Guo, Weili Dong, Xiaoxiao Fu, Jing Lin, Zhijun Dong, Xiaobo Tan, Tiemin Zhang
Pseudomonas aeruginosa (PA)-induced keratitis is a rapidly progressive ocular infectious disease that often leads to inflammatory epithelial edema, stromal infiltration, tissue destruction, corneal ulceration, and vision loss. In this study, we investigate the role of tripartite motif 8 (TRIM8) in regulating the inflammatory process of PA-induced keratitis. The expression of TRIM8 was increased in mouse corneas and in vitro-cultured macrophages after PA infection. Knockdown of the expression of TRIM8 significantly inhibited the activation of NF-κB signaling and decreased the production of pro-inflammatory cytokines both in vivo and in vitro after infected with PA...
December 19, 2016: Inflammation
https://www.readbyqxmd.com/read/27991595/pgrp-negatively-regulates-nod-mediated-cytokine-production-in-rainbow-trout-liver-cells
#8
Ju Hye Jang, Hyun Kim, Mi Jung Jang, Ju Hyun Cho
Pattern-recognition receptors (PRRs) initiate innate immunity via pathogen recognition. Recent studies suggest that signalling pathways downstream of different PRRs and their crosstalk effectively control immune responses. However, the cross-regulation among PRRs and its effects have yet to be fully described in fish. Here, we examined the crosstalk between OmPGRP-L1, a long form of PGRP in rainbow trout, and other PRRs during pathogenic infections. OmPGRP-L1 expression was increased in RTH-149 cells by iE-DAP and MDP, which are agonists of NOD1 and NOD2, respectively...
December 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27986445/nadph-oxidase-4-regulates-vascular-inflammation-in-aging-and-atherosclerosis
#9
Andrey Lozhkin, Aleksandr E Vendrov, Hua Pan, Samuel A Wickline, Nageswara R Madamanchi, Marschall S Runge
We recently reported that increased NADPH oxidase 4 (NOX4) expression and activity during aging results in enhanced cellular and mitochondrial oxidative stress, vascular inflammation, dysfunction, and atherosclerosis. The goal of the present study was to elucidate the molecular mechanism(s) for these effects and determine the importance of NOX4 modulation of proinflammatory gene expression in mouse vascular smooth muscle cells (VSMCs). A novel peptide-mediated siRNA transfection approach was used to inhibit Nox4 expression with minimal cellular toxicity...
December 14, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27981609/the-e3-ligase-trim8-targets-tak1-to-promote-insulin-resistance-and-steatohepatitis
#10
Feng-Juan Yan, Xiao-Jing Zhang, Wen-Xin Wang, Yan-Xiao Ji, Pi-Xiao Wang, Yang Yang, Jun Gong, Li-Jun Shen, Xue-Yong Zhu, Zan Huang, Hongliang Li
: Tripartite motif 8 (TRIM8), an E3 ligase ubiquitously expressed in various cells, has been previously identified to be closely involved in innate immunity. However, its role in nonalcoholic steatohepatitis (NASH) is largely unknown. Here, we report the first evidence that TRIM8 is a robust enhancer of steatohepatitis and its complications induced by a high fat diet (HFD) or a genetic deficiency (ob/ob). Using gain- and loss-of-function approaches, we observed dramatic exacerbation of insulin resistance, hepatic steatosis, inflammation, and fibrosis by hepatocyte-specific TRIM8 overexpression, whereas deletion or downregulation of TRIM8 in hepatocytes led to a completely oppose phenotype...
December 16, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27956576/tripartite-motif-8-contributes-to-pathological-cardiac-hypertrophy-through-enhancing-transforming-growth-factor-%C3%AE-activated-kinase-1-dependent-signaling-pathways
#11
Lijuan Chen, Jia Huang, Yan-Xiao Ji, Fanghua Mei, Pi-Xiao Wang, Ke-Qiong Deng, Xi Jiang, Genshan Ma, Hongliang Li
Tripartite motif (TRIM) 8 functions as an E3 ubiquitin ligase, interacting with and ubiquitinating diverse substrates, and is implicated in various pathological processes. However, the function of TRIM8 in the heart remains largely uncharacterized. This study aims to explore the role of TRIM8 in the development of pathological cardiac hypertrophy. Mice and isolated neonatal rat cardiomyocytes overexpressing or lacking TRIM8 were examined in several experiments. The effect of aortic banding-induced cardiac hypertrophy was analyzed by echocardiographic, pathological and molecular analyses...
December 12, 2016: Hypertension
https://www.readbyqxmd.com/read/27934954/strap-acts-as-a-scaffolding-protein-in-controlling-the-tlr2-4-signaling-pathway
#12
Hyunbin D Huh, Eun A Ra, Taeyun A Lee, Sujin Kang, Areum Park, Eunhye Lee, Junhee L Choi, Eunji Jang, Ji Eun Lee, Sungwook Lee, Boyoun Park
The WD40-repeat protein serine/threonine kinase receptor-associated protein (STRAP) is involved in the regulation of several biological processes, including cell proliferation and apoptosis, in response to various stresses. Here, we show that STRAP is a new scaffold protein that functions in Toll-like receptor (TLR)-mediated immune responses. STRAP specifically binds transforming growth factor β-activated kinase 1 (TAK1) and IκB kinase alpha (IKKα) along with nuclear factor-κB (NF-κB) subunit p65, leading to enhanced association between TAK1, IKKα, and p65, and subsequent facilitation of p65 phosphorylation and nuclear translocation...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27890916/polydatin-ameliorates-staphylococcus-aureus-induced-mastitis-in-mice-via-inhibiting-tlr2-mediated-activation-of-the-p38-mapk-nf-%C3%AE%C2%BAb-pathway
#13
Kang-Feng Jiang, Gan Zhao, Gan-Zhen Deng, Hai-Chong Wu, Nan-Nan Yin, Xiu-Ying Chen, Chang-Wei Qiu, Xiu-Li Peng
Recent studies show that Polydatin (PD) extracted from the roots of Polygonum cuspidatum Sieb, a widely used traditional Chinese remedies, possesses anti-inflammatory activity in several experimental models. In this study, we investigated the anti-inflammatory effects of PD on Staphylococcus aureus-induced mastitis in mice and elucidated the potential mechanisms. In mice with S aureus-induced mastitis, administration of PD (15, 30, 45 mg/kg, ip) or dexamethasone (Dex, 5 mg/kg, ip) significantly suppressed the infiltration of inflammatory cells, ameliorated the mammary structural damage, and inhibited the activity of myeloperoxidase, a biomarker of neutrophils accumulation...
November 28, 2016: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/27883089/hydrogen-sulfide-and-or-ammonia-reduces-spermatozoa-motility-through-ampk-akt-related-pathways
#14
Yong Zhao, Wei-Dong Zhang, Xin-Qi Liu, Peng-Fei Zhang, Ya-Nan Hao, Lan Li, Liang Chen, Wei Shen, Xiang-Fang Tang, Ling-Jiang Min, Qing-Shi Meng, Shu-Kun Wang, Bao Yi, Hong-Fu Zhang
A number of emerging studies suggest that air pollutants such as hydrogen sulfide (H2S) and ammonia (NH3) may cause a decline in spermatozoa motility. The impact and underlying mechanisms are currently unknown. Boar spermatozoa (in vitro) and peripubertal male mice (in vivo) were exposed to H2S and/or NH3 to evaluate the impact on spermatozoa motility. Na2S and/or NH4Cl reduced the motility of boar spermatozoa in vitro. Na2S and/or NH4Cl disrupted multiple signaling pathways including decreasing Na(+)/K(+) ATPase activity and protein kinase B (AKT) levels, activating Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and phosphatase and tensin homolog deleted on chromosome ten (PTEN), and increasing reactive oxygen species (ROS) to diminish boar spermatozoa motility...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27872270/hiv-glycoprotein-gp120-impairs-fast-axonal-transport-by-activating-tak1-signaling-pathways
#15
Sarah H Berth, Nichole Mesnard-Hoaglin, Bin Wang, Hajwa Kim, Yuyu Song, Maria Sapar, Gerardo Morfini, Scott T Brady
Sensory neuropathies are the most common neurological complication of HIV. Of these, distal sensory polyneuropathy (DSP) is directly caused by HIV infection and characterized by length-dependent axonal degeneration of dorsal root ganglion (DRG) neurons. Mechanisms for axonal degeneration in DSP remain unclear, but recent experiments revealed that the HIV glycoprotein gp120 is internalized and localized within axons of DRG neurons. Based on these findings, we investigated whether intra-axonal gp120 might impair fast axonal transport (FAT), a cellular process critical for appropriate maintenance of the axonal compartment...
December 2016: ASN Neuro
https://www.readbyqxmd.com/read/27863449/il6-mediated-inflammatory-loop-reprograms-normal-to-emt-metastatic-cscs-in-pre-neoplastic-liver-of-tgf%C3%AE-deficient-%C3%AE-2sp-mice
#16
Abhisek Mitra, Jun Yan, Xueqing Xia, Shouhao Zhou, Jian Chen, Lopa Mishra, Shulin Li
Hepatocellular carcinoma (HCC) is the second-leading cause of cancer-related deaths world-wide with poor survival rate. As many as 40% of HCCs are clonal, with alteration of key tumor suppressor pathways in stem cells is the primary cause of HCC initiation. However, mechanisms that generate metastatic stem cells in pre-neoplastic liver tissue are not well understood. We hypothesized that chronic inflammation is a major driver of the transformation of genetically defective liver stem cells (LSCs) into highly metastatic liver cancer cells in premalignant liver tissue...
November 18, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27847434/novel-functional-roles-of-caspase-related-genes-in-the-regulation-of-apoptosis-and-autophagy
#17
Ju-Hyun Shin, Sang-Hyun Min
Caspases, a family of cysteine proteases, cleave substrates and play significant roles in apoptosis, autophagy, and development. Recently, our group identified 72 genes that interact with Death Caspase-1 (DCP-1) proteins in Drosophila by genetic screening of 15,000 EP lines. However, the cellular functions and molecular mechanisms of the screened genes, such as their involvement in apoptosis and autophagy, are poorly understood in mammalian cells. In order to study the functional characterizations of the genes in human cells, we investigated 16 full-length human genes in mammalian expression vectors and tested their effects on apoptosis and autophagy in human cell lines...
November 2016: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/27847407/anti-inflammatory-effects-of-traf-interacting-protein-in-rheumatoid-arthritis-fibroblast-like-synoviocytes
#18
Qing-Zhu Kong, Li-Tao Guo, Jia-Ning Yang, Yan-Fei Wang, Jing-Xin Zhao, Su-Hong Kong, Meng Zhang, Shi Yan, Yu Jin
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by inflammatory cell infiltration, synovial inflammation, and cartilage destruction. Proliferative fibroblast-like synoviocytes (FLS) play crucial roles in both propagation of inflammation and joint damage because of their production of great amount of proinflammatory cytokines and proteolytic enzymes. In this study, we investigate the role of TRAF-interacting protein (TRIP) in regulating inflammatory process in RA-FLS. TRIP expression was attenuated in RA-FLS compared with osteoarthritis- (OA-) FLS...
2016: Mediators of Inflammation
https://www.readbyqxmd.com/read/27834881/salidroside-regulates-inflammatory-response-in-raw-264-7-macrophages-via-tlr4-tak1-and-ameliorates-inflammation-in-alcohol-binge-drinking-induced-liver-injury
#19
Peng Sun, Shun-Zong Song, Shuang Jiang, Xia Li, You-Li Yao, Yan-Ling Wu, Li-Hua Lian, Ji-Xing Nan
The current study was designed to investigate the anti-inflammatory effect of salidroside (SDS) and the underlying mechanism by using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro and a mouse model of binge drinking-induced liver injury in vivo. SDS downregulated protein expression of toll-like receptor 4 (TLR4) and CD14. SDS inhibited LPS-triggered phosphorylation of LPS-activated kinase 1 (TAK1), p38, c-Jun terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Degradation of IκB-α and nuclear translocation of nuclear factor (NF)-κB were effectively blocked by SDS...
November 9, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27821647/preclinical-evaluation-of-drugs-to-block-inflammation-driven-preterm-birth
#20
Demelza J Ireland, Elizabeth A Nathan, Shaofu Li, Adrian K Charles, Lisa F Stinson, Matthew W Kemp, John P Newnham, Jeffrey A Keelan
Intrauterine inflammation, the major cause of early preterm birth, can have microbial and sterile aetiologies. We assessed in a Transwell model the anti-inflammatory efficacies of five drugs on human extraplacental membranes delivered after preterm spontaneous labour (30-34 wk). Drugs [TPCA1 (IKKβ inhibitor), 5 z-7-oxozeaenol (OxZ, TAK1 inhibitor), inhibitor of NF-κB essential modulator binding domain (iNBD), SB239063 (p38 MAPK inhibitor) and N-acetyl cysteine (free radical scavenger free radicals)] were added after 12 h equilibration to the amniotic compartment...
November 7, 2016: Innate Immunity
keyword
keyword
101526
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"